Proteomic analysis of aortic smooth muscle cell secretions reveals an association of myosin heavy chain 11 with abdominal aortic aneurysm

• Published in: American journal of physiology. Heart and circulatory physiology 2018-10, Vol.315 (4), p.H1012-H1018
• Main Authors: Yokoyama, Utako, Arakawa, Noriaki, Ishiwata, Ryo, Yasuda, Shota, Minami, Tomoyuki, Goda, Motohiko, Uchida, Keiji, Suzuki, Shinichi, Matsumoto, Masataka, Koizumi, Nobusato, Taguri, Masataka, Hirano, Hisashi, Yoshimura, Koichi, Ogino, Hitoshi, Masuda, Munetaka, Ishikawa, Yoshihiro
• Format: Article
• Language: English
• Subjects: Aneurysms; Aortic aneurysms; Biomarkers; Cardiovascular system; Cell culture; Chains; Culture media; Enzyme-linked immunosorbent assay; Hypertension; Liquid chromatography; Mass spectrometry; Mass spectroscopy; Medical disorders; Muscles; Myosin; Pathology; Patients; Proteins; Proteomics; Regression analysis; Repair; Secretions; Sensitivity analysis; Smooth muscle
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00329.2018

Abdominal aortic aneurysm (AAA) is a life-threatening disease, and no disease-specific circulating biomarkers for AAA screening are currently available. We have identified a smooth muscle cell (SMC)-specific biomarker for AAA. We cultured aneurysmal tunica media that were collected from eight patients undergoing elective open-repair surgeries. Secreted proteins in culture medium were subjected to liquid chromatography/tandem mass spectrometry. Myosin heavy chain 11 (myosin-11) was identified as a SMC-specific protein in the tunica media-derived secretions of all patients. We then examined myosin-11 protein concentrations by ELISA in plasma samples from patients with AAA ( n = 35) and age-matched healthy control subjects ( n = 34). Circulating myosin-11 levels were significantly higher in patients with AAA than control subjects. The area under the receiver-operating characteristic curve (AUC) of myosin-11 was 0.77, with a specificity of 65% at a sensitivity of 91%. Multivariate logistic regression analysis showed a significant association between the myosin-11 level and presence of AAA. When the myosin-11 level was combined with hypertension, it improved the prediction of AAA (AUC 0.88) more than hypertension per se. We then investigated the correlation between aortic diameter and circulating myosin-11 levels using AAA serum samples from patients undergoing endovascular aneurysm repair ( n = 20). Circulating myosin-11 levels were significantly correlated with maximum aortic diameter. Furthermore, changes in myosin-11 concentrations from the baseline 12 mo after endovascular aneurysm repair were associated with those in aortic diameter. These data suggest that circulating levels of myosin-11, which is a SMC-specific myosin isoform, may be useful as a biomarker for AAA. NEW & NOTEWORTHY Extensive studies have revealed that inflammation- or proteolysis-related proteins are proposed as biomarkers for abdominal aortic aneurysm (AAA). Changes in these protein concentrations are not specific for smooth muscle, which is a major part of AAA pathologies. Hence, no disease-specific circulating markers for AAA are currently available. We found, using secretome-based proteomic analysis on human AAA tunica media, that myosin heavy chain 11 was associated with AAA. Circulating myosin heavy chain 11 may be a new tissue-specific AAA marker.